1. Field of the Invention
This invention relates to new chemical compounds useful as intermediates for the preparation of compounds having valuable pharmaceutical properties. The invention particularly relates to the preparation of N-substituted amino acid intermediates useful in the preparation of Angiotensin Converting Enzyme Inhibitor (ACEI) compounds and ACEI diuretics.
Synthesis of these novel intermediates is accomplished via a simple and unexpected process in which the amino acid is acylated directly on the nitrogen without first protecting the carboxylic acid moiety and subsequently deprotecting it. The acylated amino acid is obtained in good yield.
2. Description of the Prior Art
In the prior art of preparing peptides from amino acids, it is standard procedure to protect, and render inactive, all functionalities of a given amino acid which are not directly used in the coupling process. If reactive functionalities are allowed to remain, yield will be lower and purification made difficult because of the presence of large amounts of unwanted by-products from the interaction of these functionalities.
Two types of protecting groups are usually necessary in peptide synthesis:
the C-terminal protecting groups, those groups which render the acid portion of the amino acid inactive; and
the N-terminal protecting groups, those groups which render the amine portion inactive.
After the coupling reaction of the amino acids to form the peptide chain, the terminals are deprotected.
Various compounds of the ACEI inhibitor type are prepared by this method, for example, compounds described in U.S. Pat. No. 4,496,541. Such synthesis, however, has its drawbacks notwithstanding its advantages. The steps required in protecting and deprotecting the functionalities in the amino acid renders the process rather lengthy, cumbersome and consequently expensive.
The present invention of acylating amino acids directly on the nitrogen without first protecting the carboxylic acid moiety and subsequently deprotecting it provides an elegant, clean and economically advantageous method of producing the intermediate compounds of the present invention.